Association Studies Between XRCC1, XRCC2, XRCC3 Polymorphisms and Differentiated Thyroid Carcinoma

Area of Science:

• Genetics
• Molecular Biology
• Oncology

Background:

• DNA repair pathways, including Homologous Recombination Repair (HRR) and Base Excision Repair (BER), are crucial in differentiated thyroid cancer (DTC) pathogenesis.
• Genetic variations (polymorphisms) in DNA repair genes may influence an individual's susceptibility to DTC.

Purpose of the Study:

• To investigate the association between polymorphisms in XRCC1, XRCC2, and XRCC3 DNA repair genes and the risk and progression of differentiated thyroid cancer.
• To identify specific single nucleotide polymorphisms (SNPs) and haplotypes associated with DTC.

Main Methods:

• Literature search of the NCBI database to identify eight relevant SNPs in XRCC1, XRCC2, and XRCC3 genes.
• Genotyping analysis of selected SNPs (XRCC1: rs25487, rs25489, rs1799782; XRCC2: rs3218536; XRCC3: rs1799794, rs56377012, rs1799796, rs861539).
• Statistical analysis including multivariate adjustment, subgroup analysis by histology, haplotype analysis, and gene-gene interaction analysis.

Main Results:

• The XRCC1 SNP rs25487 was associated with a decreased DTC risk (OR: 0.47).
• The XRCC1 SNP rs1799782 (TT genotype) and XRCC3 SNP rs861539 (TT genotype) were significantly associated with increased DTC risk (OR: 2.09 and 3.02, respectively).
• Gene-gene interaction analysis revealed that combined variants of XRCC1 (rs1799782) and XRCC3 (rs861539) significantly increased DTC risk (OR: 3.66).

Conclusions:

• Polymorphisms in XRCC1 (rs25487, rs1799782) and XRCC3 (rs861539) are critical factors in DTC development and progression.
• Interactions between XRCC1 and XRCC3 variants enhance susceptibility to differentiated thyroid cancer.
• Identification of these genetic markers aids in understanding DTC pathogenesis and developing targeted therapies.